Project description:This study is an open label non randomized study of hydroxychloroquine (HCQ) with histone deacetylase (HDAC) inhibitor Vorinostat in patients with advanced solid tumors to determine the maximum tolerated dose (MTD) and to evaluate the safety and antitumor activity of this drug combination.
Project description:The aim of this study is to determine the efficacy of combining the histone deacetylase (HDAC) inhibitor sodium valproate (VPA) with anti-EGFR monoclonal antibody (panitumumab or cetuximab) maintenance in the first-line treatment of patients with RAS wild type metastatic CRC.
Project description:The model predicts the inhibitory potential of small molecules against Histone deacetylase 3 (HDAC3), a relevant human target for cancer, inflammation, neurodegenerative diseases and diabetes. The authors have used a dataset of 1098 compounds from ChEMBL and validated the model using the benchmark MUBD-HDAC3.
Model Type: Predictive machine learning model.
Model Relevance: Probability that the molecule is a HDAC3 inhibitor
Model Encoded by: Sarima Chiorlu (Ersilia)
Metadata Submitted in BioModels by: Zainab Ashimiyu-Abdusalam
Implementation of this model code by Ersilia is available here:
https://github.com/ersilia-os/eos1n4b
Project description:Organic extracts of the wildtype mold species, Aspergillus nidulans, and a strain of A. nidulans where expression of the histone deacetylase (HDAC) RpdA was knocked-down. Biological triplicate of both strains are included.
Project description:Although the Arabidopsis thaliana RPD3-type histone deacetylases have been known to form SIN3 histone deacetylase complexes that are conserved in eukaryotes, it is unknown whether they also form other types of histone deacetylase complexes. Here, we performed affinity purification followed by mass spectrometry and demonstrated that the Arabidopsis RPD3-type histone deacetylases HDA6 and HDA19 can interact with several previously uncharacterized proteins and form three types of plant-specific histone deacetylase complexes, which we named SANT, ESANT, and ARID. RNA-seq indicated that HDA6 and HDA19 function together with other components of the histone deacetylase complexes and co-regulate the expression of a number of genes. HDA6 and HDA19 have been thought to repress gene transcription by histone deacetylation. We found that the histone deacetylase complexes can also repress gene expression via certain histone-deacetylation-independent mechanisms. In the mutants of the histone deacetylase complexes, the expression of a number of stress-induced genes was up-regulated. Several mutants of the histone deacetylase complexes showed severe retardation in growth. Considering that the growth retardation is thought to be a trade-off for the increase of stress tolerance, we predict that the histone deacetylase complexes identified in this study prevent overexpression of stress-induced genes and thereby ensure normal growth of plants under non-stress conditions.
Project description:Histone deacetylase 3 (HDAC3) is an epigenome-modifying enzyme that is required for normal mouse development and tissue-specific functions. In vitro, HDAC3 protein itself has minimal enzyme activity, but gains its histone deacetylation function from stable association with the conserved deacetylase activation domain (DAD) contained in nuclear receptor corepressors NCOR1 and SMRT. Here we show that HDAC3 enzyme activity is undetectable in mice bearing point mutations in the DAD of both NCOR1 and SMRT (NS-DADm), despite normal levels of HDAC3 protein. Local histone acetylation is increased, and genomic HDAC3 recruitment is reduced though not abrogated. Remarkably, the NS-DADm mice are born and live to adulthood, whereas genetic deletion of HDAC3 is embryonic lethal. These findings demonstrate that nuclear receptor corepressors are required for HDAC3 enzyme activity in vivo, and suggest that a deacetylase-independent function of HDAC3 may be required for life. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series.
Project description:Lysine acetylation is a key transcriptional activating signalling modification occurring at the flexible ends of the histone proteins within the nucleosome, which is the basic unit of chromatin. Several histone deacetylase complexes in human fine tune these modifications thereby regulating the transcriptional output of each gene. Although histone deacetylase complexes are crucial in defining transcriptional programs during cell differentiation and cell cycle the structural information and mechanisms of actions of these holoenzymes is poor. Here we present the structure of the SIN3B histone deacetylase complex in apo form and in complex with an acetyl-lysine mimic compound, showing insights into its subunit architecture, catalytic regulation, substrate recognition and targeting to cell cycle genes.
Project description:Although the Arabidopsis thaliana RPD3-type histone deacetylases have been known to form SIN3 histone deacetylase complexes that are conserved in eukaryotes, it is unknown whether they also form other types of histone deacetylase complexes. Here, we performed affinity purification followed by mass spectrometry and demonstrated that the Arabidopsis RPD3-type histone deacetylases HDA6 and HDA19 can interact with several previously uncharacterized proteins and form three types of plant-specific histone deacetylase complexes, which we named SANT, ESANT, and ARID. RNA-seq indicated that HDA6 and HDA19 function together with other components of the histone deacetylase complexes and co-regulate the expression of a number of genes. HDA6 and HDA19 have been thought to repress gene transcription by histone deacetylation. We found that the histone deacetylase complexes can also repress gene expression via certain histone-deacetylation-independent mechanisms. In the mutants of the histone deacetylase complexes, the expression of a number of stress-induced genes was up-regulated. Several mutants of the histone deacetylase complexes showed severe retardation in growth. Considering that the growth retardation is thought to be a trade-off for the increase of stress tolerance, we predict that the histone deacetylase complexes identified in this study prevent overexpression of stress-induced genes and thereby ensure normal growth of plants under non-stress conditions.